The purpose of this investigation, completed in April, 1987, was to assess the ability of heparin to promote angiogenesis in a canine model of myocardial ischemia. Ameroid devices were placed on the proximal left another descending coronary arteries (LAD) of 32 dogs, causing progressive LAD occlusion over a 2-3 week period. The left internal mammary artery (IMA) was implanted intramyocardially in the LAD zone, with the hope that collaterals would develop from the IMA to the LAD. Dogs received continuous infusions directly into the IMA starting the day of surgery and continuing for 8 weeks. Dogs were randomized to 3 treatment groups: heparin, 15 units/hr (group 1); heparin, 15 units/hr for 2 weeks, followed by 150 units/hr for 6 weeks (group 2); or saline (group 3). After 8 weeks, IMA to LAD conductance and left circumflex coronary artery (LCX) to LAD conductances were assessed during adenosine-induced vasodilation using the microsphere technique. In saline treated dogs, conductance from the IMA to the LAD was linearly related to conductance from the LCX to the LAD (R = 0.77, p less than 0.05). Thus, collaterals from both the implanted artery and the native coronary artery to the LAD area developed proportionately. Although not statistically significant, there was a tendency towards higher IMA to LAD conductance in heparin treated dogs. Thus the data suggest that the propensity for coronary collateral growth may be related to factor(s) intrinsic to each animal, and that collateral formation may be responsive to heparin. We hope that more potent interventions can more significantly enhance collateral development, and we are directing future efforts to study this possibility.